Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data obtained in experimental murine tumors and in clinical specimens of human breast cancer have suggested that the nm23 gene may function as a metastasis suppressor gene. In this report we examined the nm23 mRNA level in tumor tissue obtained from distant metastases in 33 patients with malignant melanoma. The gene was differentially expressed in the tumors with a 20-fold range in hybridization intensities. The levels of nm23 mRNA in benign nevi obtained from 12 of the 33 patients were relatively low, with a mean value of 17% of that in the melanomas. In attempts to relate the level of nm23 expression in the tumor metastases to progression of the disease, the time from biopsy of the primary tumor to the appearance of metastases was used as a clinical end point. It was found that patients developing metastases during the first 2 years after diagnosis had significantly lower levels of tumor nm23 expression (56% of the mean value) compared to patients with less aggressive disease (164%) (P < 0.0004). In concordance with previous data the association found here between low levels of nm23 mRNA and the malignant potential of melanomas suggests that the nm23 gene may be implicated in the mechanism of disease progression in some types of human cancer.
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PMID:Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. 135 24

Reduced expression and/or somatic allelic deletion of nm23 is associated with high metastatic potential in several types of rodent tumors and human breast and colorectal carcinomas. Transfection of murine nm23-1 cDNA into highly metastatic murine K-1735 TK melanoma cells results in a reduced incidence of primary tumor formation, significant reduction in tumor metastatic potential, and altered responsiveness to the cytokine, transforming growth factor beta. Here we discuss emerging concepts concerning nm23, such as its varied pattern of alteration/expression in tumor metastasis, its effect on tumorigenesis, and its possible biochemical functions.
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PMID:Tumor metastasis and nm23: current concepts. 191 Oct 39

Reduced expression of the nm23 gene in certain rodent model systems and human breast tumors has been correlated with high tumor metastatic potential. To investigate the functional effects of nm23 expression, we have transfected a constitutive murine nm23-1 expression construct into highly metastatic K-1735 TK murine melanoma cells. TK clones expressing the exogenous nm23-1 construct exhibited a reduced incidence of primary tumor formation, significant reductions in tumor metastatic potential independent of tumor cell growth, and altered responses to the cytokine transforming growth factor beta 1 in soft agar colonization assays, compared with control-transfected TK clones. In contrast, nm23-1-transfected TK clones exhibited no significant differences in intrinsic tumor cell growth, i.e., primary tumor size in vivo, anchorage-dependent growth rate in vitro, and anchorage-independent colony formation in soft agar in vitro. The data demonstrate a suppressive effect of nm23 on several aspects of the cancer process, including tumor metastasis.
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PMID:Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. 201 93

We measured nm23-H1 and nm23-H2 mRNA levels in tissues from 22 human bladder cancers and 16 renal cell carcinomas, and in 7 bladder cancer and 6 renal cancer cell lines by Northern blot and slot blot hybridization analyses. Differences in mRNA levels were evaluated in primary tumor tissues and in paired normal tissues and cell lines. Moreover, nm23 gene expression in primary tumor tissues was compared with clinicopathological features. High nm23-H1 and nm23-H2 expression was observed in cancerous areas of human bladder tissue (nm23-H1: p = 0.001, nm23-H2: p = 0.001) and bladder cancer cell lines (nm23-H1: p = 0.001, nm23-H2: p < 0.001) compared with that in normal bladder mucosa. However, mRNA levels of both nm23 genes were not associated with histological grade, pathological stage, tumor metastasis or prognosis. On the other hand, in human renal cell carcinomas, levels of both nm23 mRNAs in tumor tissues were similar to those in paired normal kidneys, but elevated in cultured cell lines (nm23-H1: p = 0.002, nm23-H2: p = 0.014). Moreover, there was a tendency towards high nm23 gene expression in grade 2 tumors compared with grade 1 (grade 1 vs grade 2, nm23-H1: p = 0.107, nm23-H2: p = 0.008; no grade 3 tumors in this study) and in high stage renal cancers (< or = stage II vs stage III < or =, nm23-H1: p = 0.023, nm23-H2: p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of nm23 gene expressions in human bladder and renal cancers. 761 95

Reduced expression of nm23 gene is implicated in high metastatic potential in a variety of malignancies. To elucidate the role of nm23 in human gastric carcinomas, we examined loss of heterozygosity (LOH) of nm23 gene by Southern blotting, nm23 mRNA expression by Northern blotting and nm23 protein expression by Western blotting as well as immunohistochemistry in both primary and metastatic tumors. LOH of nm23 gene was found in 2 (8%) out of the 23 informative gastric carcinomas. Twenty-two (84%) out of the 26 cases expressed nm23 mRNA at higher levels in primary tumor tissue than in corresponding non-neoplastic mucosa. No obvious correlation was observed between clinico-pathological features and LOH of nm23 gene or nm23 mRNA expression. On the other hand, 52% of the gastric carcinomas showed reduction of nm23 immunoreactivity in the metastatic tumor of regional lymph nodes, as compared to the primary tumor. Interestingly, 71% of the gastric carcinomas showed weaker nm23 immunoreactivity in the liver metastasis than in the primary tumor. These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.
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PMID:Reduced expression of nm23 is associated with metastasis of human gastric carcinomas. 809 3

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene. Loss of heterozygosity (LOH), and the expression of the nm23 gene were examined on matched sets of primary tumors and lymph node as well as distant metastases from colorectal carcinomas. Three (15%) of the 20 informative specimens examined showed LOH for the nm23 locus. nm23 was expressed in all the carcinomas as well as in nonneoplastic colonic mucosa at the mRNA and protein levels. Most of the carcinomas expressed the nm23 transcript at higher levels than the corresponding nonneoplastic colonic mucosa. By Western blotting, the level of nm23 protein expression in the tumors showed an inverse correlation with the tumor stage. Furthermore, distant metastatic tumors in the liver and lung showed reduced nm23 immunoreactivity in comparison with their primary tumor, although nm23 immunoreactivity was the same in the primary tumors and in local lymph node metastases. These results suggest that decreased nm23 expression may be associated with distant metastatic spread.
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PMID:Reduced expression of nm23 protein is associated with advanced tumor stage and distant metastases in human colorectal carcinomas. 809 59

In a disease where the majority of deaths occur from metastases, improvement in survival requires the integration of systemic therapies. Research efforts must continue to focus on improving case selection criteria, improving complete response proportions, and overcoming drug resistance. Recommending a single treatment plan such as radical surgery, chemotherapy, or radiation therapy for all patients with an invasive bladder cancer is rapidly becoming outdated. Case selection is being refined by focusing on both clinical and pathologic features of the tumor. The latter include evaluation of NM23 RNA levels, or DNA ploidy and T138 surface antigen expression, which have been shown to correlate with metastatic potential. The use of hematopoietic growth factors has the potential to improve both the tolerance of chemotherapy and complete response proportions, a prerequisite for cure. However, the dose response curves for most of the known active agents are not well defined, and ultimately, new agents and strategies will be required. Drug resistance is a major barrier, but as the mechanisms are unravelled, more selective therapies can be designed. For example, resistance to adriamycin and vinblastine, two of the agents in the M-VAC regimen are mediated in part by the mdr1 gene. Ongoing studies are attempting to identify prospectively those tumors with high levels of expression which may be more amenable to treatment with drugs that do not act through this mechanism. The main advantages of the neoadjuvant approach are the ability to perform an in vivo response evaluation and the potential for bladder preservation. In most cases additional therapy for the primary tumor is required as clinical understaging is a significant problem. For some patients, initial surgery with the definition of the prognosis on firm pathologic grounds may represent a better strategy. When this is the case, the recommendation for adjuvant treatment potentially limits therapy to a more restricted population of patients for whom therapy is essential, including, for example, patients with positive lymph nodes at the time of surgery. Ideally, these patients should be entered on clinical trials designed to assess the impact of these strategies survival. Only large scale randomized trials have the potential to minimize the heterogeneity of this patient population.
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PMID:Neoadjuvant versus adjuvant chemotherapy in invasive bladder cancer. 845 89

The expression of c-erB-2 and nm23 genes product were investigated immunohistochemically in 108 resected cases of early gastric cancer. The expression rate of c-erB-2 was significantly higher in the cases of submucosal cancer or in the cases with lymph node metastasis. The expression rate of c-erB-2 was higher in the metastatic tumor than in the primary tumor. There was no significant correlation between the expression of nm23 and depth of invasion. The expression rate of nm23 was lower in the cases with lymph node metastasis than in the cases without lymph node metastasis. The expression could not be found in the metastatic tumor. These results suggest that there would be correlation between the expression of c-erB-2 and depth of invasion and lymph node metastasis, and the nm23 may suppress metastatic potential in early gastric cancer.
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PMID:[Immunohistochemical analysis of c-erB-2 and nm23 expression in early gastric carcinoma]. 896 86

NM23 is a protein associated with tumor progression, expressed in all tissues and in human tumors. Reduced expression of NM23.H1 is related to high incidence of lymph node and distant metastasis or to poor prognosis of the patient in several human malignant tumors. In this study we analyze NM23 expression in non-neoplastic mammary tissues surrounding the tumoral lesions, in human mammary carcinomas and in lymph node metastasis. Our analysis shows that NM23.H1 expression is lower in the mammary cells surrounding the tumor than in the tumor itself. In the primary tumors we observed a negative trend between degree of local invasion and level of NM23.H1 expression. A further decrease of NM23.H1 was detected in the invasive tumors that metastasized to axillary lymph nodes and in the metastasis. NM23.H2 was always more highly expressed than NM23.H1, and reduced expression of NM23.H1 but not NM23.H2 was concordant with the presence of lymph node metastasis or local invasiveness of the primary tumor. A positive correlation between NM23.H1 mRNA content and cell growth rate of breast tumor cells has been confirmed. However, this trend was not maintained in cancer cells from tumors that metastasized to axillary lymph nodes and in metastatic cells; in these 2 situations the NM23.H1 mRNA content varied without any relationship to the proliferative rate of the cells. In addition, in comparison with the initial tumor, the metastatic cell population showed a strong decrease of NM23.H1 expression and increased proliferative activity.
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PMID:NM23 gene expression in human breast carcinomas: loss of correlation with cell proliferation in the advanced phase of tumor progression. 903 78

To evaluate the significance of nm23 protein expression in cervical carcinoma, 83 patients with stage IB disease, treated primarily with surgery were studied immunohistochemically. Of the cases 57 were squamous carcinoma, 9 were adenocarcinoma, 14 were adenosquamous carcinoma and 3 were small-cell carcinoma. nm23 expression was positive in 63% of the cases. Although positive expression was more common in squamous and adenosquamous type tumors, negative expression was dominant in adenocarcinoma (P<0.05). When nm23 expression was compared with the clinicopathologic risk factors, there was no correlation of expression with the grade, deep invasion of the stroma, parametrial involvement and lymph node metastasis. But expression was inversely correlated with the number of metastatic lymph nodes (P<0.05). Although 3 or more lymph node metastases is a very poor prognostic sign, nm23 expression was not correlated either with recurrence or survival. Expression was negative in 77% of metastatic lymph nodes and in all of the recurrences. The predominance of negative expression in metastatic lymph nodes (P<0.05) and recurrences seems to be related to the aggressive behavior of the negative clone in the heterogeneous primary tumor.
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PMID:nm23 expression in carcinoma of the uterine cervix. 964 Dec 40


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